Substituted thiopyridines

ABSTRACT

Substituted thiopyridines of the general formula I                    
     where 
     n is 1 or 2; 
     R 1  is chlorine, C 1 -C 3 -fluoroalkyl, nitro or methylsulfonyl; 
     R 2  is a C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl or C 2 -C 10 -alkynyl radical, in each case unsubstituted or substituted by halogen, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxycarbonyl, di-(C 1 -C 4 -alkylamino) carbonyl, cyano or nitro, a C 3 -C 8 -cycloalkyl radical, or a C 1 -C 4 -alkylenephenyl, phenyl or naphthyl radical which is unsubstituted or substituted in the phenyl moiety by halogen, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, trifluoromethyl, cyano or nitro.

This application is a 371 of PCT/EB97/04707 Aug. 29, 1997 now WO98/11072 Mar. 19, 1998.

The invention relates to novel thiopyridines of the general formula I

where

n is 1 or 2;

R¹ is chlorine, C₁-C₃-fluoroalkyl, nitro or methylsulfonyl;

R² is a C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl or C₂-C₁₀-alkynyl radical, in eachcase unsubstituted or substituted by halogen, C₁-C₄-alkoxy,C₁-C₄-alkoxycarbonyl, di-(C₁-C₄-alkylamino) carbonyl, cyano or nitro, aC₃-C₈-cycloalkyl radical, or a C₁-C₄-alkylenephenyl, phenyl or naphthylradical which is unsubstituted or substituted in the phenyl moiety byhalogen, C₁-C₃-alkyl, C₁-C₃-alkoxy, trifluoromethyl, cyano or nitro.

Moreover, the invention relates to processes for their preparation andto their use as intermediates for the preparation of herbicidally activecrop protection agents, as they are disclosed in WO-A-95/02580. Theinvention furthermore relates to the pyridine thioethers of the formulaIa, which are suitable for the preparation of the thiopyridines I, asintermediates.

2-(3-Nitrophenylthio), 2-(2-methyl-4-methoxyphenylthio) and2-(2-nitrobenzylthio)pyridines which have a further chlorine, ortrifluoromethyl or methylsulfonyl radical, in the 5-position and achlorine substituent in the 3-position have already been disclosed inthe literature (EP 320 448, J5 6029-504, EP 498 396). 3-Fluoropyridineswhich are correspondingly substituted are disclosed in U.S. Pat. No.4,983,211.

The thiopyridines mentioned in the above publications are used asherbicides or fungicides, or as intermediates for herbicides, thefunction which is responsible for the herbicidal action in the endmolecule being synthesized in each case via the thio substituent, whichthus remains in the end molecule.

It is an object of the present invention to provide novel thiopyridinederivatives which are suitable as coupling components for thepreparation of substituted phenylpyridines as they are described inWO-A-95/02580. Here, the thio substituent acts as a leaving group.

It is a further object of the present invention to provide a processwhich makes the desired thiopyridines accessible in high yields.

Accordingly, we have found the thiopyridines defined at the outset, ofthe general formula I

where

n is 1 or 2;

R¹ is chlorine, C₁-C₃-fluoroalkyl, nitro or methylsulfonyl;

R² is a C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl or C₂-C₁₀-alkynyl radical, in eachcase unsubstituted or substituted by halogen, C₁-C₄-alkoxy,C₁-C₄-alkoxycarbonyl, di-(C₁-C₄-alkylamino)carbonyl, cyano or nitro, aC₃-C₈-cycloalkyl radical, or a C₁-C₄-alkylenephenyl, phenyl or naphthylradical which is unsubstituted or substituted in the phenyl moiety byhalogen, C₁-C₃-alkyl, C₁-C₃-alkoxy, trifluoromethyl, cyano or nitro.

The meanings mentioned above for the substituent R² in formula I arecollective terms for individual enumerations of the individual groupmembers. All carbon chains, ie. all alkyl, alkenyl, alkynyl or alkoxymoieties, can be straight-chain or branched. Halogenated substituentspreferably have attached to them 1-6 identical or different halogenatoms.

Examples of individual meanings are:

halogen fluorine, chlorine, bromine and iodine, preferably fluorine andchlorine;

C₁-C₃-alkyl methyl, ethyl, n-propyl, 1-methylethyl;

C₁-C₁₀-alkyl C₁-C₃-alkyl as mentioned above, and also n-butyl,1-methylpropyl, 2-methylpropyl and 1,1-dimethylethyl, n-pentyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl,2-ethylbutyl, 1,1,2-trimethylpropyl, 1-ethyl-1-methylpropyl and1-ethyl-2-methylpropyl; n-heptyl, n-octyl, n-nonyl, n-decyl,1-methylhexyl, 1-ethylhexyl, 1-methylheptyl, 1-methyloctyl,1-methylnonyl;

C₂-C₁₀-alkenyl ethenyl, prop-1-en-1-yl, prop-2-en-1-yl, 1-methylethenyl,n-buten-1-yl, n-buten-2-yl, n-buten-3-yl, 1-methylprop-1-en-1-yl,2-methylprop-1-en-1-yl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl,n-penten-1-yl, n-penten-2-yl, n-penten-3-yl, n-penten-4-yl,1-methylbut-1-en-1-yl, 2-methylbut-1-en-1-yl, 3-methylbut-1-en-1-yl,1-methylbut-2-en-1-yl, 2-methylbut-2-en-1-yl, 3-methylbut-2-en-1-yl,1-methylbut-3-en-1-yl, 2-methylbut-3-en-1-yl, 3-methylbut-3-en-1-yl,1,1-dimethylprop-2-en-1-yl, 1,2-dimethylprop-1-en-1-yl,1,2-dimethylprop-2-en-1-yl, 1-ethylprop-1-en-2-yl,1-ethylprop-2-en-1-yl, n-hex-1-en-1-yl, n-hex-2-en-1-yl,n-hex-3-en-1-yl, n-hex-4-en-1-yl, n-hex-5-en-1-yl,1-methylpent-1-en-1-yl, 2-methylpent-1-en-1-yl, 3-methylpent-1-en-1-yl,4-methylpent-1-en-1-yl, 1-methylpent-2-en-1-yl, 2-methylpent-2-en-1-yl,3-methylpent-2-en-1-yl, 4-methylpent-2-en-1-yl, 1-methylpent-3-en-1-yl,2-methylpent-3-en-1-yl, 3-methylpent-3-en-1-yl, 4-methylpent-3-en-1-yl,1-methylpent-4-en-1-yl, 2-methylpent-4-en-1-yl, 3-methylpent-4-en-1-yl,4-methylpent-4-en-1-yl, 1,1-dimethylbut-2-en-1-yl,1,1-dimethylbut-3-en-1-yl, 1,2-dimethylbut-1-en-1-yl,1,2-dimethylbut-2-en-1-yl, 1,2-dimethylbut-3-en-1-yl,1,3-dimethylbut-1-en-1-yl, 1,3-dimethylbut-2-en-1-yl,1,3-dimethylbut-3-en-1-yl, 2,2-dimethylbut-3-en-1-yl,2,3-dimethylbut-1-en-1-yl, 2,3-dimethylbut-2-en-1-yl,2,3-dimethylbut-3-en-1-yl, 3,3-dimethylbut-1-en-1-yl,3,3-dimethylbut-2-en-1-yl, 1-ethylbut-1-en-1-yl, 1-ethylbut-2-en-1-yl,1-ethylbut-3-en-1-yl, 2-ethylbut-1-en-1-yl, 2-ethylbut-2-en-1-yl,2-ethylbut-3-en-1-yl, 1,1,2-trimethylprop-2-en-1-yl,1-ethyl-1-methylprop-2-en-1-yl, 1-ethyl-2-methylprop-1-en-1-yl and1-ethyl-2-methylprop-2-en-1-yl, hept-2-en-1-yl, oct-2-en-1-yl,non-2-en-1-yl, dec-2-en-1-yl, preferably ethenyl and prop-2-en-1-yl;

C₂-C₁₀-alkynyl ethynyl and C₃-C₆-alkynyl such as prop-1-yn-1-yl,prop-2-yn-3-yl, n-but-1-yn-1-yl, n-but-1-yn-4-yl, n-but-2-yn-1-yl,n-pent-1-yn-1-yl, n-pent-1-yn-3-yl, n-pent-1-yn-4-yl, n-pent-1-yn-5-yl,n-pent-2-yn-1-yl, n-pent-2-yn-4-yl, n-pent-2-yn-5-yl,3-methylbut-1-yn-1-yl, 3-methyl-but-1-yn-3-yl, 3-methyl-but-1-yn-4-yl,n-hex-1-yn-1-yl, n-hex-1-yn-3-yl, n-hex-1-yn-4-yl, n-hex-1-yn-5-yl,n-hex-1-yn-6-yl, n-hex-2-yn-1-yl, n-hex-2-yn-4-yl, n-hex-2-yn-5-yl,n-hex-2-yn-6-yl, n-hex-3-yn-1-yl, n-hex-3-yn-2-yl,3-methylpent-1-yn-1-yl, 3-methyl-pent-1-yn-3-yl, 3-methylpent-1-yn-4-yl,3-methylpent-1-yn-5-yl, 4-methylpent-1-yn-1-yl, 4-methylpent-2-yn-4-yland 4-methylpent-2-yn-5-yl, hept-2-yn-1-yl, oct-2-yn-1-yl,non-2-yn-1-yl, dec-2-yn-1-yl, preferably prop-2-yn-1-yl,1-methylprop-2-yn-1-yl;

C₁-C₃-fluoroalkyl C₁-C₃-alkyl as mentioned above, where in each case 1-5hydrogen atoms are replaced by fluorine, eg. fluoromethyl,difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl,2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl,3,3,3-trifluoropropyl, preference is given to difluoromethyl,trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl,3,3,3-trifluoropropyl, special preference is given to trifluoromethyl;

C₁-C₁₀-haloalkyl C₁-C₁₀-alkyl as mentioned above, where in each case 1-6hydrogen atoms are replaced by fluorine, chlorine and/or bromine, ie.,for example, chloromethyl, dichloromethyl, trichloromethyl,fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl,dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl,2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and3-chloropropyl, preferably trifluoromethyl;

C₂-C₁₀-haloalkenyl C₂-C₁₀-alkenyl as mentioned above, where in each case1-6 hydrogen atoms are replaced by fluorine, chlorine and/or bromine;

C₂-C₁₀-haloalkynyl C₂-C₁₀-alkynyl as mentioned above, where in each caseone to six hydrogen atoms are replaced by fluorine, chlorine and/orbromine;

C₃-C₈-cycloalkyl cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl and cyclooctyl, preferably cyclopropyl, cyclopentyl andcyclohexyl;

cyano-(C₁-C₂)-alkyl C₁-C₁₀-alkyl as mentioned above, where in each caseone hydrogen atom is replaced by the cyano group, ie., for example,cyanomethyl, 1-cyanoeth-1-yl, 2-cyanoeth-1-yl, 1-cyanoprop-1-yl,2-cyanoprop-1-yl, 3-cyanoprop-1-yl, 1-cyanoprop-2-yl, 2-cyanoprop-2-yl,1-cyanobut-1-yl, 2-cyanobut-1-yl, 3-cyanobut-1-yl, 4-cyanobut-1-yl,1-cyanobut-2-yl, 2-cyanobut-2-yl, 1-cyanobut-3-yl, 2-cyanobut-3-yl,1-cyano-2-methyl-prop-3-yl, 2-cyano2-methyl-prop-3-yl,3-cyano-2-methyl-prop-3-yl, and 2-cyanomethyl-prop-2-yl,6-cyanohex-1-yl, 7-cyanohept-1-yl, 8-cyanooct-1-yl, 9-cyanonon-1-yl,10-cyanodec-1-yl; preferably cyanomethyl, 1-cyano-1-methylethyl;

C₁-C₄-alkoxy and the alkoxy moieties of C_(l)-C₄-alkoxycarbonyl,methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy,2-methylpropoxy and 1,1-dimethyl-ethoxy, preferably methoxy, ethoxy and1-methylethoxy; di-(C₁-C₄-alkyl)aminocarbonyl N,N-dimethylaminocarbonyl,N,N-diethylaminocarbonyl, N,N-dipropylaminocarbonyl,N,N-di-(1-methylethyl)aminocarbonyl, N,N-dibutylaminocarbonyl,N,N-di-(1-methylpropyl)aminocarbonyl,N,N-di-(2-methylpropyl)aminocarbonyl,N,N-di-(1,1-dimethylethyl)aminocarbonyl, N-ethyl-N-methylaminocarbonyl,N-methyl-N-propylaminocarbonyl, N-methyl-N-(1-methylethyl)aminocarbonyl,N-butyl-N-methylaminocarbonyl, N-methyl-N-(1-methylpropyl)aminocarbonyl,N-methyl-N-(2-methylpropyl)aminocarbonyl,N-(1,1-di-methylethyl)-N-methylaminocarbonyl,N-ethyl-N-propylaminocarbonyl, N-ethyl-N-(1-methylethyl)aminocarbonyl,N-butyl-N-ethylaminocarbonyl, N-ethyl-N-(1-methylpropyl)aminocarbonyl,N-ethyl-N-(2-methylpropyl)aminocarbonyl,N-ethyl-N-(1,1-dimethylethyl)aminocarbonyl,N-(1-methylethyl)-N-propylaminocarbonyl, N-butyl-N-propylaminocarbonyl,N-(1-methylpropyl)-N-propylaminocarbonyl,N-(2-methylpropyl)-N-propylamino-carbonyl,N-(1,1-dimethylethyl)-N-propylaminocarbonyl,N-butyl-N-(-methylethyl)aminocarbonyl,

N-(1-methylethyl)-N-(1-methylpropyl)aminocarbonyl,N-(1-methylethyl)-N-(2-methylpropyl)aminocarbonyl,N-(1,1-dimethylethyl)-N-(1-methylethyl)aminocarbonyl,N-butyl-N-(1-methylpropyl)aminocarbonyl,N-butyl-N-(2-methylpropyl)aminocarbonyl,N-butyl-N-(1,1-dimethylethyl)aminocarbonyl,N-(1-methylpropyl)-N-(2-methylpropyl)aminocarbonyl,N-(1,1-dimethylethyl)-N-(1-methylpropyl)aminocarbonyl andN-(1,1-dimethylethyl)-N-(2-methylpropyl)aminocarbonyl, preferablydimethylaminocarbonyl and diethylaminocarbonyl;

C₁-C₄-alkylene methylene, ethylene, propylene, 1-methylethylene,butylene, 1,2-dimethylethylene and 1-ethylethylene;

1-phenyl which is unsubstituted or substituted by halogen, C₁-C₃-alkyl,C₁-C₃-alkoxy, trifluoromethyl, cyano or nitro 2-, 3-, 4-chlorophenyl,2-, 3-, 4-tolyl, 2-chloro-4-methylphenyl, 2,4-dichlorophenyl,2,4,6-trichlorophenyl, 2,6-dichloro-4-methyl-phenyl, 2-, 3-,4-methoxyphenyl, 2-chloro-4-methoxyphenyl, 3-chloro-4-methoxyphenyl, 2-,3-, 4-trifluoromethylphenyl, 2-, 3-, 4-cyanophenyl, 2-, 3-,4-nitrophenyl, 2-methyl-4-nitrophenyl, 2-chloro-4-trifluoromethylphenyl,2-chloro-4-nitrophenyl and unsubstituted phenyl.

Preferred amongst the compounds I are those where

n is 1 or 2;

R¹ is chlorine, nitro or C₁-C₃-fluoroalkyl;

R² is a C₁-C₈-alkyl, C₂-C₈-alkenyl or C₃-C₈-alkynyl radical,unsubstituted or substituted by halogen or C₁-C₄-alkoxy, anunsubstituted C₃-C₈-cycloalkyl radical, or a benzyl or phenyl radical,unsubstituted or substituted in the phenyl moiety by halogen,C₁-C₃-alkyl, C₁-C₃-alkoxy, nitro, cyano or trifluoromethyl.

Especially preferred compounds I are those where

n is 1 or 2;

R¹ is chlorine, trifluoromethyl or difluoromethyl;

R² is a C₁-C₈-alkyl radical, unsubstituted or substituted by chlorine ormethoxy, or a benzyl or phenyl radical, unsubstituted or substituted inthe phenyl moiety by chlorine, methyl, methoxy or trifluoromethyl.

Individual examples which may be mentioned are the following pyridinethioethers Ia of Tables 1-4, the pyridine sulfoxides Ib of Tables 5-8and the pyridine sulfones Ic of Tables 9-12.

Preferred are the pyridine thioethers I.001-1.116 of the formula Ia1

which are given in Table 1.

TABLE 1 No. R² Ia1.001 CH₃ Ia1.002 C₂H₅ Ia1.003 n-C₃H₇ Ia1.004 i-C₃H₇Ia1.005 n-C₄H₉ Ia1.006 sec-C₄H₉ Ia1.007 i-C₄H₉ Ia1.008 tert-C₄H₉ Ia1.009n-C₅H₁₁ Ia1.010 sec-C₅H₁₁ Ia1.011 CH₂—CH₂—CH(CH₃)₂ Ia1.012CH₂—CH(CH₃)—CH₂—CH₃ Ia1.013 CH(CH₃)—CH(CH₃)₂ Ia1.014 CH(C₂H₅)₂ Ia1.015n-C₆H₁₃ Ia1.016 sec-C₆H₁₃ Ia1.017 CH(C₂H₅)-n-C₃H₇ Ia1.018CH(CH₃)—CH(CH₃)—C₂H₅ Ia1.019 n-C₇H₁₅ Ia1.020 sec-C₇-H₁₅ Ia1.021CH(C₂H₅)-n-C₄H₉ Ia1.022 CH(CH₃)—CH(CH₃)-n-C₃H₇ Ia1.023 n-C₈H₁₇ Ia1.024sec-C₈H₁₇ Ia1.025 CH(C₂H₅)-n-C₅H₁₁ Ia1.026 n-C₉H₁₉ Ia1.027 sec-C₉H₁₉Ia1.028 CH(C₂H₅)-n-C₆H₁₃ Ia1.029 n-C₁₀H₂₁ Ia1.030 sec-C₁₀H₂₁ Ia1.031CH₂—CH₂—O—CH₃ Ia1.032 CH₂—CH₂—O—C₂H₅ Ia1.033 CH₂—CH(OCH₃)—CH₃ Ia1.034(CH₂)₃—O—CH₃ Ia1.035 (CH₂)₃—O—C₂H₅ Ia1.036 (CH₂)₄—O—CH₃ Ia1.037 CH₂CH₂ClIa1.038 (CH₂)₃Cl Ia1.039 (CH₂)₄Cl Ia1.040 cyclopropyl Ia1.041 cyclobutylIa1.042 cyclopentyl Ia1.043 cyclohexyl Ia1.044 cycloheptyl Ia1.045cyclooctyl Ia1.046 CH₂═CH₂ Ia1.047 CH₂—CH ═CH₂ Ia1.048 CH₂CH═CH—CH₃Ia1.049 CH(CH₃)—CH═CH₂ Ia1.050 CH₂—CH₂—C(CH₃)═CH₂ Ia1.051 CH₂CH═C(CH₃)₂Ia1.052 C(CH₃)₂—CH═CH₂ Ia1.053 CH₂—C≡CH Ia1.054 CH₂—C≡C—CH₃ Ia1.055CH(CH₃)—C≡CH Ia1.056 C(CH₃)₂—C≡CH Ia1.057 C(C≡CH)—CH(C₂H₅)-n-C₄H₉Ia1.058 CH₂—CH₂—CN Ia1.059 (CH₂)₃CN Ia1.060 CH₂CH₂NO₂ Ia1.061 (CH₂)₃NO₂Ia1.062 phenyl Ia1.063 2-chlorophenyl Ia1.064 3-chlorophenyl Ia1.0654-chlorophenyl Ia1.066 2,3-dichlorophenyl Ia1.067 2,4-dichlorophenylIa1.068 2,5-dichlorophenyl Ia1.069 2,6-dichlorophenyl Ia1.0702,4,6-trichlorophenyl Ia1.071 2-tolyl Ia1.072 3-tolyl Ia1.073 4-tolylIa1.074 2-chloro-4-tolyl Ia1.075 2,6-dichloro-4-tolyl Ia1.0764-chloro-2-tolyl Ia1.077 4,6-dichloro-2-tolyl Ia1.078 2-methoxyphenylIa1.079 3-methoxyphenyl Ia1.080 4-methoxyphenyl Ia1.0812-chloro-4-methoxyphenyl Ia1.082 2,6-dichloro-4-methoxyphenyl Ia1.0834-chloro-2-methoxyphenyl Ia1.084 4,6-dichloro-2-methoxyphenyl Ia1.0852-nitrophenyl Ia1.086 3-nitrophenyl Ia1.087 4-nitrophenyl Ia1.0884-methyl-2-nitrophenyl Ia1.089 4-chloro-2-nitrophenyl Ia1.0904-methoxy-2-nitrophenyl Ia1.091 2-trifluoromethylphenyl Ia1.0923-trifluoromethylphenyl Ia1.093 4-trifluoromethylphenyl Ia1.0942-chloro-4-trifluoromethylphenyl Ia1.0954-chloro-2-trifluoromethylphenyl Ia1.096 2-cyanophenyl Ia1.0973-cyanophenyl Ia1.098 4-cyanophenyl Ia1.099 2-methyl-4-nitrophenylIa1.100 5-methyl-2-nitrophenyl Ia1.101 1-naphthyl Ia1.102 2-naphthylIa1.103 4-methyl-1-naphthyl Ia1.104 4-chloro-1-naphthyl Ia1.105 benzylIa1.106 2-methylbenzyl Ia1.107 3-methylbenzyl Ia1.108 4-methylbenzylIa1.109 2-chlorobenzyl Ia1.110 3-chlorobenzyl Ia1.111 4-chlorobenzylIa1.112 2,4-dichlorobenzyl Ia1.113 2,4,6-trichlorobenzyl Ia1.1142-trifluoromethylbenzyl Ia1.115 3-trifluoromethylbenzyl Ia1.1164-trifluoromethylbenzyl

TABLE 2 Furthermore preferred are the pyridine thioethersIa2.001-Ia2.085 and Ia2.087-Ia2.116 of the formula Ia2, which differfrom the compounds Ia1.001-Ia1.085 and Ia1.087-Ia1.116 in that, insteadof chlorine, a trifluoromethyl group is attached to the pyridine ring inthe 5 -position.

Ia2

TABLE 2 Furthermore preferred are the pyridine thioethersIa2.001-Ia2.085 and Ia2.087-Ia2.116 of the formula Ia2, which differfrom the compounds Ia1.001-Ia1.085 and Ia1.087-Ia1.116 in that, insteadof chlorine, a trifluoromethyl group is attached to the pyridine ring inthe 5 -position.

Ia2

TABLE 2 Furthermore preferred are the pyridine thioethersIa2.001-Ia2.085 and Ia2.087-Ia2.116 of the formula Ia2, which differfrom the compounds Ia1.001-Ia1.085 and Ia1.087-Ia1.116 in that, insteadof chlorine, a trifluoromethyl group is attached to the pyridine ring inthe 5 -position.

Ia2

TABLE 2 Furthermore preferred are the pyridine thioethersIa2.001-Ia2.085 and Ia2.087-Ia2.116 of the formula Ia2, which differfrom the compounds Ia1.001-Ia1.085 and Ia1.087-Ia1.116 in that, insteadof chlorine, a trifluoromethyl group is attached to the pyridine ring inthe 5 -position.

Ia2

TABLE 6 Furthermore preferred are the thiopyridines Ib2.001-Ib2.116 ofthe formula Ib2, which differ from the compounds Ia2.001-Ia2.116 in thatthe corresponding sulfoxides are present.

Ib2

TABLE 6 Furthermore preferred are the thiopyridines Ib2.001-Ib2.116 ofthe formula Ib2, which differ from the compounds Ia2.001-Ia2.116 in thatthe corresponding sulfoxides are present.

Ib2

TABLE 6 Furthermore preferred are the thiopyridines Ib2.001-Ib2.116 ofthe formula Ib2, which differ from the compounds Ia2.001-Ia2.116 in thatthe corresponding sulfoxides are present.

Ib2

TABLE 9 Furthermore preferred are the thiopyridines Icl. 001-Icl. 116 ofthe formula Icl, which differ from the compounds Ia1.001-Ia1.116 in thatthe corresponding sulfones are present.

Ic1

TABLE 9 Furthermore preferred are the thiopyridines Icl. 001-Icl. 116 ofthe formula Icl, which differ from the compounds Ia1.001-Ia1.116 in thatthe corresponding sulfones are present.

Ic1

TABLE 9 Furthermore preferred are the thiopyridines Icl. 001-Icl. 116 ofthe formula Icl, which differ from the compounds Ia1.001-Ia1.116 in thatthe corresponding sulfones are present.

Ic1

TABLE 9 Furthermore preferred are the thiopyridines Icl. 001-Icl. 116 ofthe formula Icl, which differ from the compounds Ia1.001-Ia1.116 in thatthe corresponding sulfones are present.

Ic1

Furthermore, processes have been found with which the thiopyridines ofthe formula I can be prepared in surprisingly high yields.

The thiopyridines I are especially preferably obtained when substituted3-chloro-2-halopyridines of the formula II

where R¹ has the abovementioned meaning and Hal is fluorine, chlorine orbromine are reacted, in a first step, with a thio compound of theformula III

H[O]_(m)S(═O)_(n)—R²  III

where R² has the abovementioned meaning and m and n are 0, or with analkali metal or alkaline earth metal salt thereof, in the presence orabsence of a base, first to give a pyridene thioether of the formula Iaand the latter is then oxidized stepwise to the sulfoxide Ib

or sulfone Ic, or when the 3-chloro-2-halopyridines of the formula IIare directly reacted with a sulfinic acid of the formula III, where R²has the abovementioned meaning and m and n are 1, or with an alkalimetal or alkaline earth metal salt thereof, in the presence or absenceof a base, to give the pyridylsulfones of the formula Ic. A substancewhich is especially preferably employed as compound II is2,3-dichloro-5-trifluoromethylpyridine, which is commercially available.

The synthesis of the compounds I is demonstrated by way of example bythe reaction described in the scheme below, which starts with2,3-dichloro-5-trifluoromethylpyridine and propylmercaptan sodium saltas nucleophile, using hydrogen peroxide as the oxidant:

Instead of hydrogen peroxide, peracetic acid or chlorine and bromine mayalso be used as the oxidant in a method similar to the above equation.

In accordance with a further variant, the compounds I can be preparedstarting from 2,3-dichloro-5-trifluoromethylpyridine and abenzenesulfinic acid salt as the nucleophile, as described in the schemebelow:

Preferred embodiments of the process are given hereinbelow:

The reaction of the 3-chloro-2-halopyridines II with a thiol III (m,n=0)or with a sulfinic acid III (m,n=1) is advantageously carried out in thepresence of a solvent from −20 to 200° C., preferably 10-180° C.,particularly preferably from 10 to 80° C. for the thiol and from 80 to180° C. for the sulfinic acid.

Solvents which are used for these reactions are—depending on thetemperature range—hydrocarbons such as pentane, hexane, cyclohexane,heptane, toluene, xylene, chlorinated hydrocarbons such as methylenechloride, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, chlorobenzene,1,2-, 1,3- or 1,4-dichlorobenzene, ethers such as diethyl ether, methyltert-butyl ether, tetrahydrofuran, 1,3- or 1,4-dioxane, anisole, glycolethers such as dimethyl glycol ether, diethyl glycol ether, diethyleneglycol dimethyl ether, esters such as ethyl acetate, propyl acetate,methyl isobutyrate, isobutyl acetate, carboxamides such as DMF,N-methylpyrrolidone, nitrohydrocarbons such as nitromethane,nitroethane, nitropropane and nitrobenzene, ureas such astetraethylurea, tetrabutylurea, dimethylethyleneurea,dimethylpropyleneurea, sulfoxides such as dimethyl sulfoxide, sulfonessuch as dimethyl sulfone, diethyl sulfone, tetramethylene sulfone,nitriles such as acetonitrile, propionitrile, butyronitrile orisobutyronitrile; water, or else mixtures of these up to a two-phasesystem. The process may also be carried out according to the inventionin the melt, without the addition of a solvent.

The molar ratios at which the starting compounds are reacted with eachother are generally 0.9-1.4, preferably 0.95-1.1, for the ratio ofthiol, or sulfinic acid, to 3-chloro-2-halopyridine II. Theconcentration of the starting materials in the solvent is 0.1-5 mol/l,preferably 0.2-2 mol/l.

The thiols, or sulfinic acids, are expediently employed in the form oftheir alkali metal or alkaline earth metal salts, ie. their lithium,sodium, potassium, magnesium or calcium salts. However, the reaction canalso be carried out in the presence of an organic base, eg.triethylamine, tri-n-propylamine, N-ethyl-diisopropylamine, pyridine,α-, β-, γ-picoline, 2,4-, 2,6-lutidine, N-methylpyrrolidine,triethylenediamine, dimethylaniline, N,N-dimethylcyclohexylamine,quinoline or acridine. In addition, it is also possible to bind thehydrogen halide which is eliminated during the reaction by adding analkali metal hydride, alkali metal hydrogencarbonate, alkali metalcarbonate, alkaline earth metal hydride, alkaline earth metalhydrogencarbonate or alkaline earth metal carbonate of theabovementioned metals. The thiols, or sulfinic acids, are advantageouslyconverted into their corresponding salts using one of the abovementionedbases in an inert solvent, to be followed by the reaction with the3-chloro-2-halopyridine. Depending on the reactivity of the sulfurderivatives used, the water formed during salt formation may be left inthe reaction medium, or else removed azeotropically with a solvent. Saltformation may also be carried out in an aqueous phase to start with,whereupon the water is removed. The salt formation may also be carriedout with an alkali metal hydride, alkali metal alkoxide, alkaline earthmetal hydride or alkaline earth metal alkoxide, preferably sodiummethoxide or sodium ethoxide, and the excess alcohol removed prior tothe reaction with the pyridine.

Finally, the reaction can also be carried out in an aqueous two-phasesystem, preferably in the presence of phase-transfer catalysts, such asquaternary ammonium or phosphonium salts. The reaction conditionsdescribed in EP-A-556 737 are suitable for the two-phase reaction.

It is advantageous to add the 3-chloro-2-halopyridine II to a mixture ofthe thiol III or the sulfinic acid III or the respective salt in one ofthe abovementioned solvents at from 10 to 80° C. in the course of 0.25-2hours and to stir for a further 0.5 to 16 hours, preferably 2 to 8hours, at from 10 to 80° C. in the case of the thiol respectively atfrom 80 to 180° C. in the case of the sulfinic acid so as to completethe reaction.

However, it is also possible to add the thiol III or the sulfinic acidIII together or, via separate feeding, in parallel with the addition ofthe base to the 3-chloro-2-halopyridine II and then to finish thereaction as above.

When using an aqueous two-phase system, the starting materials II andIII can be added to a mixture of the phase-transfer catalyst in the twophases in any sequence, with stirring, and then the reaction can befinished in the abovementioned temperature range with an addition ofbase.

The reaction can be carried out under atmospheric pressure orsuperatmospheric pressure, continuously or batchwise.

The pyridine thioethers of the formula Ia can be oxidized to thethiopyridines I preferably by means of hydrogen superoxide,approximately equivalent amounts of oxidant giving the pyridinesulfoxides Ib and approximately twice the molar amounts giving thepyridine sulfones Ic.

Solvents which can be used are, for example, water, acetonitrile,carboxylic acids such as acetic acid, trifluoroacetic acid, propionicacid, alcohols such as methanol, ethanol, isopropanol, tert-butanol,chlorinated hydrocarbons such as methylene chloride,1,1,2,2-tetrachloroethane or ketones such as acetone or methyl ethylketone. Especially preferred are water, methanol, acetic acid andtrifluoroacetic acid.

In an especially preferred variant, the reaction can also be catalyzedby adding stronger acids such as trifluoroacetic acid or perchloricacid. However, metal compounds are also suitable as catalysts, eg.transition metal oxides such as vanadium pentaoxide, sodium tungstate,potassium dichromate, iron oxide tungstate, sodium tungstate molybdicacid, osmic acid, titanium trichloride, selenium dioxide,phenyleneselenic acid, oxovanadinyl 2,4-pentanedionate.

The catalysts are generally employed in an amount of from 0.5 to 10%,but it is also possible to employ stoichiometric amounts due to the factthat the inorganic catalysts are readily filtered off and recovered.

A further preferred oxidant is peracetic acid or hydrogensuperoxide/acetic anhydride, if appropriate also the peracetic acidwhich exists in equilibrium with a hydrogen superoxide/acetic acidmixture.

Another preferred oxidant is trifluoroperacetic acid, or the mixturehydrogen superoxide/trifluoroacetic acid, or else the mixture hydrogenperoxide/trifluoroacetic anhydride.

In general, oxidation with hydrogen superoxide in glacial acetic acid ishighly selective, but frequently slow. In general, the reaction time canbe shortened by adding trifluoroacetic acid (cf. Synthesis Example 5,Variant a and b). The oxidation with hydrogen peroxide in puretrifluoroacetic acid frequently leads to the formation of thecorresponding N-oxides, as described, inter alia, in Chimia 29 (1975)466. Rapid and selective oxidation of the pyridine thioethers Ia to thecorresponding sulfoxides Ib and sulfones Ic is successfully carried outfor example with solutions of hydrogen superoxide in mixtures of aceticacid and trifluoroacetic acid in a volumetric ratio of 10:1 to 1:1, inparticular 6:1 to 4:1. These mixtures are therefore especially preferredas solvents.

Solvents which can furthermore be used are petroleum ether, theabovementioned solvents, and the abovementioned catalysts.

In addition to peracetic acid and trifluoroperacetic acid, it is alsopossible to employ perbenzoic acid, monoperphthalic acid or3-chloroperbenzoic acid, expediently in chlorinated hydrocarbons such asmethylene chloride or 1,2-dichloroethane.

Highly suitable for the oxidation of the thiols to sulfoxides orsulfones are furthermore chlorine and bromine. Advantageous solvents arewater, acetonitrile, dioxane, two-phase systems such as aqueouspotassium hydrogen carbonate solution/dichloromethane and, in the caseof pyridine alkyl thioethers, also acetic acid.

Other substances which can be employed as sources of active halogen aretert-butyl hypochlorite, hypochlorous and hypobromous acid, their salts,and furthermore N-halogen compounds such as N-bromo- andN-chlorosuccinimide, or else sulfuryl chloride.

Other substances which are advantageous for the oxidation are dinitrogentetraoxide, eg. in the technologically simple variant with air/nitrogendioxide or nitrogen trioxide and, for example, osmium(VIII) oxide ascatalyst. In addition, the oxidation can also be carried out directlywith nitric acid, suitable additional solvents being acetic anhydride,acetic acid, and suitable catalysts being copper(I) bromide, copper(I)chloride, copper(II) bromide and copper(II) chloride.

Also suitable for the oxidation is photo-sensitized oxygen transfer,recommended photosensitizers being chlorophyll, protoporphyrin, rosebengal or methylene blue. Suitable inert solvents are hydrocarbons suchas pentane, hexane, heptane, cyclohexane, chlorinated hydrocarbons suchas methylene chloride, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane,alcohols such as methanol, ethanol, n-propanol or isopropanol, ketonessuch as acetone, methyl ethyl ketone, polar aprotic solvents such asacetonitrile, propionitrile or aromatic hydrocarbons such as benzene,toluene, chlorobenzene or xylene. Instead of oxygen, it is also possibleto use ozone in the abovementioned solvents, and additionally alsoethers, 1,4-dioxane or THF.

In addition to photosensitization, it is also recommended to usecatalysts for the oxidation, for example oxides and sulfides of nickel,copper, aluminum, tungsten, chromium, vanadium, ruthenium, titanium,manganese, molybdenum, magnesium and iron.

Depending on the stoichiometry of the oxidants used, the result iseither the pyridine sulfoxides Ib or their pyridine sulfones Ic. Themolar ratios in which the starting compounds are reacted with each otherare generally 0.9-1.8, preferably 1.05-1.3 for the ratio of pyridinethioether Ia to oxidant in the case of the oxidation to the pyridinesulfoxide, and generally 1.9-3.5, preferably 2.05-2.9, in the case ofthe oxidation to the pyridine sulfone.

The concentration of starting materials in the solvent is generally0.1-5 mol/l, preferably 0.2-2 mol/l.

It is advantageous to introduce the pyridine thioether or the pyridinesulfoxide, if appropriate together with one of the above-mentionedcatalysts, into one of the abovementioned solvents and then to add theoxidant in the course of 0.25-20 hours, with stirring. The addition andreaction temperature depend on the optimal efficacy of the oxidants inquestion and the avoidance of secondary reactions. If photosensitizedoxygen is used, the process is generally carried out at from −20 to 80°C., but if metal catalysis is used, the process is generally carried outat from 50 to 140° C., and when ozone is used generally at from −78 to60° C. Due to the limited solubility of the oxygen derivatives, theyhave to be passed continuously into the reaction mixture over aprolonged period (up to 20 hours) until oxidation on the sulfoxide orsulfone level is complete. If air/nitrogen dioxide or nitrogen trioxideis used, the process is preferably carried out at from 15-150° C. in thecourse of 1-15 hours. Liquid or readily soluble oxidants such ashydrogen peroxide, peracetic acid, or trifluoroperacetic acid, which isformed together with acetic anhydride or in equilibrium with acetic acidand/or trifluoroperacetic acid, respectively, or hypochlorous acid orhypobromous acid, tert-butyl hypochlorite, chlorine or bromine,N-chloro-, or N-bromosuccinimide or nitric acid can be added to thereaction mixture of the pyridine thioether or pyridine sulfoxide withinshorter periods in the course of 0.25-6 hours, depending on theexothermal character of the reaction, to complete the reaction after afurther 1-60 hours. Also preferred is a staggered addition of the liquidor dissolved oxidant. In the case of hydrogen superoxide and peraceticacid, or trifluoro-peracetic acid, the process is generally carried outat 0-90° C., if tert-butyl hypochlorite is used, generally at from −-78to 30° C., if N-halogen compounds are used, in general at 0-30° C. andif nitric acid is used in general at from 20 to 140° C. In the case ofchlorine or bromine, a reaction temperature of 0-40° C. is recommended.

The oxidation reactions can be carried out under atmospheric pressure orunder elevated pressure, continuously or batchwise.

The thiopyridines I according to the invention are valuable precursorsfor the preparation of crop protection agents, in particular herbicidesfrom the class of the phenylpyridines, as they are described in WO-A95/02580.

An especially advantageous process for the preparation of herbicidalphenylpyridines based on the thiopyridines I according to the inventionis described in a parallel application, DE Application No. 196 36995.9(see Diagram 1). In addition, the thiopyridines I can also be used asintermediates in organic syntheses theses for the preparation ofpharmaceuticals, colors and the like.

SYNTHESIS EXAMPLES Example 13-Chloro-2-n-propylthio-5-trifluoromethylpyridine

23.8 g (0.313 mol) of 1-propanethiol were added in the course of 30minutes to a mixture of 7.9 g (0.313 mol) of 95% pure sodium hydride in200 ml of THF while flushing with nitrogen and stirring, a temperatureof 25-30° C. being maintained by means of cooling. After the mixture hadbeen stirred for 1 hour, 54 g (0.25 mol) of2,3-dichloro-5-trifluoromethylpyridine in 50 ml THF were added at 25-30°C. in the course of 20 minutes with stirring, and stirring was continuedfor 10 hours at 23° C. The reaction mixture was concentrated in vacuo,taken up in methylene chloride, extracted with 0.5 N sodium hydroxidesolution, dried over magnesium sulfate and concentrated, yielding 63.5 g(99.4%) of the title compound of n_(D) ²³=1.5120.

Example 2 3-Chloro-2-phenylthio-5-trifluoromethylpyridine

Variant a

Starting from 7.9 g (0.313 mol) of sodium hydride, 34.4 g (0.313 mol) ofthiophenol and 54 g (0.25 mol) of2,3-dichloro-5-trifluoromethylpyridine, 72.4 g (100% of theory) of thetitle compound of n_(D) ²⁴=1.5750 were obtained under the conditions ofExample 1.

Variant b

108 g (0.981 mol) of thiophenol were added at 20-25° C. with stirring inthe course of 1 hour to a mixture of 78.48 g (0.981 mol) of 50% strengthsodium hydroxide solution and 800 ml of toluene. After the water hadbeen removed under reflux conditions, 207.45 g (0.9316 mol) of 97% pure2,3-dichloro-5-trifluoromethylpyridine were added at 80-50° C. in thecourse of 30 minutes with stirring to the suspension of the above sodiumthiophenolate, and stirring was continued for 1 hour at 50° C. and 1hour at 60° C. The reaction mixture was washed in succession with water,0.5 N sodium hydroxide solution and with water, dried over sodiumsulfate and concentrated in vacuo. This gave 276.2 g of the titlecompound of n_(D) ²⁴=1.5740 which, according to GC analysis, contained aremainder of 2.9% of toluene;

Yield 268.2 g (99% of theory)

Example 3 3-Chloro-2-n-propylsulfinyl-5-trifluoromethylpyridine

8.4 g (0.124 mol) of 50% strength hydrogen peroxide were added withstirring at 15-20° C. in the course of 15 minutes to a mixture of 31 g(0.1213 mol) of 3-chloro-2-n-propylthio-5-trifluoromethylpyridine in 150ml of acetic acid, during which process the temperature rose to 27° C.in the course of 6 hours. After the reaction mixture had been stirredfor 14 hours at 25° C., it was poured into ice-water and extracted 3times with methylene chloride. The organic phase was washed with waterand saturated sodium hydrogen carbonate solution, dried and concentratedin vacuo, yielding 32 g (97.2% of theory) of the title compound of m.p.51-53° C.

Example 4 3-Chloro-2-n-propylsulfonyl-5-trifluoromethylpyridine

11.7 g (0.172 mol) of 50% strength hydrogen peroxide were added at20-25° C. in the course of 30 minutes with stirring to 20 g (0.0783 mol)of 3-chloro-2-n-propylthio-5-trifluoromethylpyridine in 150 ml ofglacial acetic acid, during which process the temperature climbed up to31° C. in the course of 8 hours. After the reaction mixture had beenstirred for 60 hours, during which process it cooled to 25° C., it waspoured into ice-water and worked up as described. This gave 21 g (93.3%of theory) of the title compound of m.p. 41-42° C.

Example 5 3-Chloro-2-phenylsulfinyl-5-trifluoromethylpyridine

Variant a

6.2 g (0.09 mol) of 50% strength hydrogen superoxide were added at 24°C. in the course of 10 minutes with stirring to a mixture of 22.5 g(0.077 mol) of 3-chloro-2-phenylthio-5-trifluoromethylpyridine in 150 mlof glacial acetic acid, during which process the temperature climbed upto 30° C. in the course of 4 hours. The reaction mixture was stirred for14 hours at 30-25° C., then poured into ice-water and worked up asdescribed. This gave 24.6 g of a viscous oil which, according to HPLCcheck, contained 19.9 g (83.5% of theory) of the title compound and 1.4g (5.6% of theory) of the corresponding sulfone. Chromatography withmethylene chloride through a suction filter with flash silica gelyielded the pure title compound (18.2 g=76.6% of theory) of m.p. 79-80°C.

Variant b

11.76 g (0.173 mol) of 50% strength hydrogen superoxide were added at25° C. in the course of 20 minutes to a mixture of 50 g (0.173 mol) of3-chloro-2-phenylthio-5-trifluoromethylpyridine in 50 ml oftrifluoroacetic acid and 250 ml of acetic acid. After the reactionmixture has been stirred at 30 to 28° C. for 4 hours, it was extractedwith methylene chloride, and the organic phase was washed with sodiumhydrogen carbonate solution and with water. Drying over magnesiumsulfate and concentration in vacuo yielded 48.5 g of colorless crystalsof m.p. 67-68° C. According to NMR analysis, they contained 44.9 g (85%of theory) of the pure title compound and 3.6 g (6.4% of theory) of thecorresponding sulfone.

Example 6 3-Chloro-2-phenylsulfonyl-5-trifluoromethylpyridine

Variant a

25.1 g (0.369 mol) of 50% strength hydrogen superoxide were added at 35°C. in the course of 30 minutes with stirring to a mixture of 48.5 g(0.1675 mol) of 3-chloro-2-phenylthio-5-trifluoromethylpyridine in 300ml of glacial acetic acid and stirred for 18 hours at 40° C. until theexothermal reaction had subsided to 25° C. After HPLC check of thecourse of the reaction, a further 5 g (0.0735 mol) of 50% strengthhydrogen superoxide were added and the mixture was stirred for 2 hoursat 40° C. The reaction mixture was poured into ice-water and worked upas described. This gave 49.2 g of the title compound as a crude oilwhich, after chromatography with methylene chloride through silica gel,solidified to give 44.5 g (82.6% of theory) of colorless crystals ofm.p. 87-88° C.

Variant b

273.2 g (0.495 mol) of 13.5% strength sodium hypochlorite solution in240 ml of water were added at 25-30° C. in the course of 2 hours to amixture of 65.2 g (0.225 mol) of3-chloro-2-phenylthio-5-trifluoromethylpyridine in 100 ml of water and100 ml of glacial acetic acid. After the mixture had been stirred for 2hours at 25° C., a further 70 ml of glacial acetic acid were added, and84.5 g (0.153 mol) of 13.5% strength sodium hypochlorite solution werefed in over 30 minutes. After the reaction mixture had been stirred for3 hours at 25° C., it was extracted with methylene chloride, and theorganic extract was washed with water, saturated sodium hydrogencarbonate solution and again with water. The mixture was subsequentlydried over magnesium sulfate and concentrated in vacuo. This gave 70.9 g(98% of theory) of the title compound of m.p. 91° C. According to GCcheck, the purity was 100%.

The protocols given in the above Synthesis Examples were used forobtaining further pyridine thioethers Ia and thiopyridines I bymodifying the starting compounds as required. Selected physical data ofthe pyridine thioethers are listed in Table 10 and of the thiopyridinesin Table 11.

TABLE 10 No. R¹ R² n_(D) ²⁴ Fp [° C.] Ia2.003 CF₃ n-C₃H₇ 1.5120 Ia2.008CF₃ tert-C₄H₉ 1.5069 Ia2.015 CF₃ n-C₆H₁₃ 1.5031 Ia2.029 CF₃ n-C₁₀H₂₁1.4930 Ia2.062 CF₃ phenyl 1.5750 Ia2.065 CF₃ 4-chlorophenyl 63-65Ia2.073 CF₃ 4-tolyl 1.5725 Ia2.080 CF₃ 4-methoxyphenyl 81-83 Ia2.105 CF₃benzyl 1.5645 Ic4.062 CF₂H phenyl 50-53 Ic5.062 NO₂ phenyl 103-104

TABLE 10 No. R¹ R² n_(D) ²⁴ Fp [° C.] Ia2.003 CF₃ n-C₃H₇ 1.5120 Ia2.008CF₃ tert-C₄H₉ 1.5069 Ia2.015 CF₃ n-C₆H₁₃ 1.5031 Ia2.029 CF₃ n-C₁₀H₂₁1.4930 Ia2.062 CF₃ phenyl 1.5750 Ia2.065 CF₃ 4-chlorophenyl 63-65Ia2.073 CF₃ 4-tolyl 1.5725 Ia2.080 CF₃ 4-methoxyphenyl 81-83 Ia2.105 CF₃benzyl 1.5645 Ic4.062 CF₂H phenyl 50-53 Ic5.062 NO₂ phenyl 103-104

Use Example

3-Chloro-2-phenylsulfonyl-5-trifluoromethylpyridine was stirred with4-chloro-2-fluoro-5-methoxyphenylmagnesium bromide for 2.5 hours at roomtemperature in THF. Working-up by distillation gave the coupling product2-(4-chloro-2-fluoro-5-methoxyphenyl)-3-chloro-5-trifluoromethylpyridinein a yield of 84%, which is outstanding.

Further herbicidally active ingredients disclosed in WO 95/02580 areobtained in a simple manner by eliminating the methoxy group in the5-position on the benzene ring and other, prior-art subsequentreactions.

We claim:
 1. A process for the preparation of thiopyridines of theformula Ib

where R¹ is chlorine, trifluoromethyl or difluoromethyl; R² is aC₁-C₈-alkyl radical which is unsubstituted or substituted by chlorine ormethoxy, or a benzyl or phenyl radical which is unsubstituted orsubstituted in the phenyl moiety by chlorine, methyl, methoxy ortrifluoromethyl; said process comprising reacting a3-chloro-2-halopyridine of the formula II

where hal is fluorine, chlorine or bromine, with a thio compound of theformula III HSR²   III or an alkali metal or alkaline earth metal saltthereof, in the presence of trifluoracetic acid or perchloric acid, togive the pyridine thioether Ia,

and subsequently treating the latter with an oxidant.
 2. A process asclaimed in claim 1, wherein the oxidation of the pyridine thioethers Iato give the thiopyridines Ib is effected with the aid of hydrogenperoxide in a mixture of acetic acid and trifluoroacetic acid in a ratioof 6:1 to 4:1 by volume.
 3. A process as claimed in claim 1, wherein theoxidation of the pyridine thioethers Ia to give the thiopyridines Ib iseffected with the aid of hypochlorous acid and an alkali metal saltthereof.